title: Tailored vaccines targeting the elderly using whole inactivated influenza vaccines bearing cytokine immunomodulators.
abstract: Influenza and its complications disproportionately affect the elderly, leading to high morbidity and mortality in this ever-increasing population. Despite widespread vaccination efforts, the current influenza vaccines are less effective in the elderly; hence newer vaccine strategies are needed to improve their efficacy in this age group. We have previously shown that co-presentation of cytokines on the surface of inactivated influenza virus particles affords better protection from lethal homotypic viral challenge in young adult mice than conventional non-adjuvanted whole inactivated vaccine. Here, we determined the efficacy of these vaccine formulations in Balb/c mice "aged" to 17 months ("aged mice") along with the addition of a membrane-bound interleukin-12 (IL-12) vaccine formulation. Our investigations found that a single low-dose intramuscular vaccination with inactivated whole influenza vaccine co-presenting IL-12 was sufficient to provide enhanced protection from subsequent influenza challenge as compared with non-adjuvanted whole inactivated vaccine. Our results indicate that incorporation of cytokines such as IL-12 in a membrane-bound formulation in whole inactivated vaccine may provide a means to lower the vaccine dose while eliciting enhanced protective responses in the elderly, an age group that responds poorly to current vaccination regimens.
authors.affiliation: 1 Department of Biomedical Sciences and Pathobiology, Virginia Tech , Blacksburg, Virginia.
authors.forename: Tila
authors.initials: T
authors.lastname: Khan
authors.forename: Connie L
authors.initials: CL
authors.lastname: Heffron
authors.forename: Kevin P
authors.initials: KP
authors.lastname: High
authors.forename: Paul C
authors.initials: PC
authors.lastname: Roberts
mesh_terms: D000368:Aged; D000375:Aging / Q000276:immunology*; D000818:Animals; D006801:Humans; D007110:Immunity, Active; D056747:Immunomodulation; D007252:Influenza Vaccines; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D029521:Alphainfluenzavirus / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D032541:Mass Vaccination / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D044382:Population Groups; D057285:Precision Medicine; D019076:Transgenes / Q000235:genetics; D014771:Virion / Q000276:immunology / Q000378:metabolism*
chemical_list: D007252:Influenza Vaccines; D018664:Interleukin-12